Aa
victrelis after failed incivek ?
I just completed week 18 of incivek triple treatment. Viral load test just came back as detected, but not quantifiable. I was undetectable since week 8.
My Dr. said this is a fail and wanted me to stop treatment. I asked him if it would be possible for me to immediately start on a new triple treatment with Victrelis. He thought it was an interesting idea, and is submitting it to insurance now.
The idea was to try the new treatment while the viral load is still so low, instead of waiting between treatments for the viral load to increase back up to a large number.
Has anyone else here heard of someone trying this ? Or heard of any reason not to do this.
I was diagnosed about 15 years ago. Geno 1a. Back then I started with a fibrosis of 1, but I know have cirrhosis. This was my third try at treatment.
I am not sure if there would be any advantage to stopping treatment for 3 or six months and then starting on victrelis.
Since I already have cirrhosis I am not sure that there is any reason for me to wait, and a lot of reason to try and clear as soon as possible.
I know there are new treatments on the horizon, but they are probably still years from approval. Victrelis is approved now, so why not try it ?
I do not want to try any type of research study that might have me on a placebo for a year. Unless I am sure I am getting the actual treatment, there is no way I would go through months of interferon/riba.
Wow this really *****. I had been so hopeful that it was working this time around.
Was diagnosed over 2
My Dr. said this is a fail and wanted me to stop treatment. I asked him if it would be possible for me to immediately start on a new triple treatment with Victrelis. He thought it was an interesting idea, and is submitting it to insurance now.
The idea was to try the new treatment while the viral load is still so low, instead of waiting between treatments for the viral load to increase back up to a large number.
Has anyone else here heard of someone trying this ? Or heard of any reason not to do this.
I was diagnosed about 15 years ago. Geno 1a. Back then I started with a fibrosis of 1, but I know have cirrhosis. This was my third try at treatment.
I am not sure if there would be any advantage to stopping treatment for 3 or six months and then starting on victrelis.
Since I already have cirrhosis I am not sure that there is any reason for me to wait, and a lot of reason to try and clear as soon as possible.
I know there are new treatments on the horizon, but they are probably still years from approval. Victrelis is approved now, so why not try it ?
I do not want to try any type of research study that might have me on a placebo for a year. Unless I am sure I am getting the actual treatment, there is no way I would go through months of interferon/riba.
Wow this really *****. I had been so hopeful that it was working this time around.
Was diagnosed over 2
You know Hector, the fact that any remaining virus develops resistance following failed treatment is a material and relevant fact that all treaters should disclose to prospective patients. It factors in to the "treat now or not treat?" equation.
I don't think they do. I didn't know it until reading a (yours, I think) prior post.
After going through hep c treatment and finding this Med Help after the fact (too bad!), I will undergo no medical treatments in the future w/o consulting MedHelp and the posters thereon.
We need MedHelp bumper stickers.
I don't think they do. I didn't know it until reading a (yours, I think) prior post.
After going through hep c treatment and finding this Med Help after the fact (too bad!), I will undergo no medical treatments in the future w/o consulting MedHelp and the posters thereon.
We need MedHelp bumper stickers.
I took triple combo w/victrelis.. was undetected by week 8 week 12 and end of treatment . took a viral load test 2 weeks ago (4 1/2 months since end of treatment) came back with a viral load of 10,000 I relapsed.. Docs advise is in 2+ years hopefully 7977 will be approved, or we look for a clinical trial. meanwhile back to the same old same old follow ups.. I am trying to get over the shock and get on with life, but its tough
Very sorry to hear that you've most likely had a breakthrough.. I went through the same thing on Incivek, however I never did reach UND, down to 52 (ish) at week 12. I was tested every 4 weeks and week 16 showed a slight increase in count but the doc and I decided to go until week 20 to see what that showed. It was up over 1,000 at week 20, therefore, treatment was stopped. Very discouraging to say the least. If I were you I would definitely get another PCR just to make sure...ya just never know! It's been 8 months since I stopped, feeling a lot better except the rash has yet to go away completely. Hang in there!
Best of luck to you to~ I am reading so many good things about the GS 7977, better and more encouraging news, everyday.
Make sure to take care of yourself, with kid-gloves, and keep yrself in the best shape possible, for the Interferon free Tx, just around the corner.
Take care of your liver, by avoiding toxic chemicals, even anti-freeze vapors, and gasoline, are toxic, any chemical you can smell, or touch to your skin.
There are many good meds out here, to help with cirrhosis, if problems crop up for you. We have so many knowledgable people on this site, that know all about cirrhosis, and which meds to take, for what, etc.
You are doing a great job, you are doing everything possible, to take the best care for yourself, so give yourself a pat on the back.
Make sure to take care of yourself, with kid-gloves, and keep yrself in the best shape possible, for the Interferon free Tx, just around the corner.
Take care of your liver, by avoiding toxic chemicals, even anti-freeze vapors, and gasoline, are toxic, any chemical you can smell, or touch to your skin.
There are many good meds out here, to help with cirrhosis, if problems crop up for you. We have so many knowledgable people on this site, that know all about cirrhosis, and which meds to take, for what, etc.
You are doing a great job, you are doing everything possible, to take the best care for yourself, so give yourself a pat on the back.
Thanks to everyone for your responses and support.
It is disappointing, but I guess it was not unexpected considering the odds of SVR for me.
Some more info for those who asked.
I had asked my Dr. to do monthly PCR testing so that if I did have a breakthrough I would know as soon as possible. The idea was to not do any more weeks of treatment then I absolutely had to. So the week 18 is not a standard testing point, but once you have a breakthrough that is a fail.
My cirrhosis was determined by biopsy about 2 years ago. It was my third biopsy, with the fibrosis increasing on each. The first ten years I was diagnosed I had almost know progression, but the past five years it went from 2 to 4.
Best of luck to everyone
It is disappointing, but I guess it was not unexpected considering the odds of SVR for me.
Some more info for those who asked.
I had asked my Dr. to do monthly PCR testing so that if I did have a breakthrough I would know as soon as possible. The idea was to not do any more weeks of treatment then I absolutely had to. So the week 18 is not a standard testing point, but once you have a breakthrough that is a fail.
My cirrhosis was determined by biopsy about 2 years ago. It was my third biopsy, with the fibrosis increasing on each. The first ten years I was diagnosed I had almost know progression, but the past five years it went from 2 to 4.
Best of luck to everyone
Offwarranty, I would also ask for a re-test soon, and I agree doing Vic would be out.......... Wishing you the best.
Idyllic, those are just treatment guidelines. A pcr can be given at anytime and a breakthrough trumps all.
On-treatment failure includes subjects who met a protocol-defined virologic stopping rule or who had detectable HCV-RNA at the time of their last dose of INCIVEK and subjects who had viral breakthrough on peginterferon alfa/ribavirin.
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htm
Bill from the above study, this was overall.
On-treatment virologic failures
7% (26/363)
Idyllic, those are just treatment guidelines. A pcr can be given at anytime and a breakthrough trumps all.
On-treatment failure includes subjects who met a protocol-defined virologic stopping rule or who had detectable HCV-RNA at the time of their last dose of INCIVEK and subjects who had viral breakthrough on peginterferon alfa/ribavirin.
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htm
Bill from the above study, this was overall.
On-treatment virologic failures
7% (26/363)
What percentage of responders who are undetectable at 4 or 12 weeks go to experience a breakthrough?
I still do not quite follow the reason the course of your treatment was determined on week 18 labs rather than week 24.
The treatment guidelines:
If HCV RNA is ≥ 1000 IU/mL at Week 4 or 12 or detectable at Week 24, all therapy is stopped.
The treatment guidelines:
If HCV RNA is ≥ 1000 IU/mL at Week 4 or 12 or detectable at Week 24, all therapy is stopped.
I love your username - it is exactly how I feel! I'm just writing to say how very sorry I am about these results! I know it must be truly a horrible feeling. I do agree with all the other comments. Get a repeat PCR test before quitting tx, then if you do have to quit I wish you all the best in finding another tx to try soon. I'm on week 42 of 48 with Incivek triple tx, and I'm also cirrhotic, so I'm also thinking a bit about how I will handle it if the virus returns after tx ends. I would also want to avoid any placebos! Many of the trials now seem to use variations on drugs that might be more or less effective or sx-prone, rather than drugs versus placebo, and that sounds better to me. Good luck, and keep us posted.
I agree with Frontrange Mom. Week 18 isn't really a make or break milestone with Incivek. I thought for the purpose of assessing response-guided therapy eligibility at weeks 4 and 12 you had to have a VL under 1000. I thought you do not have to be UND until week 24 with Incivek. I get you had a PCR in between but the rules of Futility really only address weeks 4, 12 & 24.
I am not sure I am encouraging you to hang in there if you are detectible but ..well here is the link:
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htm
I am sorry to have hung in there this long to have a lab come back Det. I know how devastating it must be. When was the last time you had a biopsy? I was just wondering how you know you have Cirrhosis. Your fibrosis may not be progressing as rapidly as it must seem.
Unfortunately the others are right once you treat with one PI taking the other is not really an option. I would be very surprised if your insurance covered the Vic after paying for 12 weeks of Incivek.
I guess after having a re-test to be sure you are Detectible the best thing to do is heal. Flush all the drugs from your system and work on getting in shape and getting your life back. There are all kinds of meds on the horizon, I know it seems like they will take forever to be released but you can work on staying healthy between now and then.
Take care and be well.
I am not sure I am encouraging you to hang in there if you are detectible but ..well here is the link:
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htm
I am sorry to have hung in there this long to have a lab come back Det. I know how devastating it must be. When was the last time you had a biopsy? I was just wondering how you know you have Cirrhosis. Your fibrosis may not be progressing as rapidly as it must seem.
Unfortunately the others are right once you treat with one PI taking the other is not really an option. I would be very surprised if your insurance covered the Vic after paying for 12 weeks of Incivek.
I guess after having a re-test to be sure you are Detectible the best thing to do is heal. Flush all the drugs from your system and work on getting in shape and getting your life back. There are all kinds of meds on the horizon, I know it seems like they will take forever to be released but you can work on staying healthy between now and then.
Take care and be well.
Perhaps there is a Clinical Research Study you could participate in, while your vl is still low, along with your enzymes, etc.
I agree with everyone's comments above. If you were UND since week 8, but show DET not quantifiable now at week 18, the likelihood is that you have had a viral breakthrough. You could ask your doc to continue treatment for a few more weeks and re-test at 20 or 24 weeks. Chances are you have had a breakthrough and that will be confirmed with DET quantifiable in a few weeks. We can always hope, but chances are it's a breakthrough. I know this is disappointing news to take, but if it is a breakthrough, then it does no good to continue. Incivek probably worked for you, but then when you completed Incivek, Interferon didn't work well enough to get rid of the last more resistant strains of your virus.
From what I understand, you cannot treat with Victrellis once you've treated with Incivek, due to the fact that they are similar drugs and if you have developed resistance to one, you will have resistance to the other as well.
Advocate1955
From what I understand, you cannot treat with Victrellis once you've treated with Incivek, due to the fact that they are similar drugs and if you have developed resistance to one, you will have resistance to the other as well.
Advocate1955
I didn't think that 18 weeks is a go/no go test point for Incivek. I'd ask for a retest and/or wait for your 24 week results.
I am very sorry to hear this news. I know it must be devastating.
The first thing I would do if I was you is to get a redraw of the viral load. It is possible the lab made an error and, if you are stopping Tx, you would want to know for sure that the VL is truly detectable and not a lab error.
If you have treated with one protease inhibitor (in your case, Incivek) retreating with the other protease inhibitor (Vic.), is not recommended because the drugs are very similar, so if you develop resistance to one, you will probably have resistance to the other.
Perhaps you could get into a clinical trial with drugs that are not similar to Inc. and Vic.
Here is an excellent slide presentation concerning Hep C and resistance:
http://74.43.177.57/courses/2010/pg/pawlotsky/player.html
And this article discusses resistance issues with the PIs and the treatment futility rules:
http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/HCV%20New%20Agents/Module/Practical_Guide/Pages/Page%205.aspx
Here are a couple of paragraphs from the last article:
"On-Treatment Management: Futility Rules and Prevention of Resistance"
"Viral resistance with boceprevir and telaprevir occurs because of the selection of preexisting variants during the course of therapy, as a result of failure to eradicate infection on triple combination treatment.[54] In pooled analyses of subjects who had on-treatment failure or relapse during clinical trials with boceprevir or telaprevir, HCV variants emerged, which have been shown to carry several NS3 amino acid substitutions that reduce viral susceptibility to boceprevir and telaprevir (Table 10).[51,53] Extensive cross-resistance exists between the 2 drugs, one of several reasons why they should never be used together. Patterns of treatment-emergent amino acid substitutions were genotype 1 subtype specific. Resistance was found to be more frequent among previous null responders and among those with subtype 1a HCV. The emergence of different substitutions among the subtypes can be explained by a different genetic barrier to resistance between subtype 1a and subtype 1b. For example, coding for R155K requires a single-nucleotide change in subtype 1a (AGG → AAG) but 2 nucleotide changes in subtype 1b (CGG → AAG). Thus, R155K is more likely to preexist in subtype 1a than in subtype 1b. The higher failure rates of boceprevir- or telaprevir-based therapy that are observed in treatment-experienced patients are owing to a poorer response to pegIFN/RBV than in treatment-naive patients, resulting in the subsequent outgrowth of resistant variants selected by boceprevir or telaprevir. "
"The clinical implications of treatment failure to boceprevir- or telaprevir-based therapy are unknown. In theory, the persistence of resistant variants could lead to patients being ineligible for, or unresponsive to, future regimens that incorporate PIs into novel regimens. Several lines of evidence and reasoning provide reassurance on this issue. First, HCV is not known to be capable of archiving its genome as do HIV or hepatitis B virus. Data suggest that after treatment withdrawal, treatment-emergent substitutions decline in relative abundance over time and that wild-type virus regains its predominance in the majority of cases.[55-57] However, this may take 2-3 years, and subtype 1a tends to return to wild type more slowly. Moreover, the diversity of antiviral agents under development may overcome whatever adverse impact viral variants that are resistant to boceprevir or telaprevir might confer. Ultimately, trials in patients who have failed boceprevir or telaprevir therapy will be critical in addressing this question.
The panel underscored the importance of assessing the indications for treatment (particularly in null responders—weighing risk of treatment failure and resistance with need for therapy), adherence to stopping rules to minimize the risk of emergence of resistant variants, and any potential impact on future treatment options. For both drugs, the stopping rules put forth in the prescribing information have been harmonized for treatment-naive and treatment-experienced patients. Of note, the HCV RNA cutoffs used for boceprevir and telaprevir stopping rules differ. .....
Currently, there is no evidence to support switching from one PI to the other if treatment is not successful. The safety and efficacy of switching to the other PI because of a drug-specific adverse event also has not been established. Likewise, a patient for whom one PI was not successful should not be retreated with a regimen containing the other PI."
The first thing I would do if I was you is to get a redraw of the viral load. It is possible the lab made an error and, if you are stopping Tx, you would want to know for sure that the VL is truly detectable and not a lab error.
If you have treated with one protease inhibitor (in your case, Incivek) retreating with the other protease inhibitor (Vic.), is not recommended because the drugs are very similar, so if you develop resistance to one, you will probably have resistance to the other.
Perhaps you could get into a clinical trial with drugs that are not similar to Inc. and Vic.
Here is an excellent slide presentation concerning Hep C and resistance:
http://74.43.177.57/courses/2010/pg/pawlotsky/player.html
And this article discusses resistance issues with the PIs and the treatment futility rules:
http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/HCV%20New%20Agents/Module/Practical_Guide/Pages/Page%205.aspx
Here are a couple of paragraphs from the last article:
"On-Treatment Management: Futility Rules and Prevention of Resistance"
"Viral resistance with boceprevir and telaprevir occurs because of the selection of preexisting variants during the course of therapy, as a result of failure to eradicate infection on triple combination treatment.[54] In pooled analyses of subjects who had on-treatment failure or relapse during clinical trials with boceprevir or telaprevir, HCV variants emerged, which have been shown to carry several NS3 amino acid substitutions that reduce viral susceptibility to boceprevir and telaprevir (Table 10).[51,53] Extensive cross-resistance exists between the 2 drugs, one of several reasons why they should never be used together. Patterns of treatment-emergent amino acid substitutions were genotype 1 subtype specific. Resistance was found to be more frequent among previous null responders and among those with subtype 1a HCV. The emergence of different substitutions among the subtypes can be explained by a different genetic barrier to resistance between subtype 1a and subtype 1b. For example, coding for R155K requires a single-nucleotide change in subtype 1a (AGG → AAG) but 2 nucleotide changes in subtype 1b (CGG → AAG). Thus, R155K is more likely to preexist in subtype 1a than in subtype 1b. The higher failure rates of boceprevir- or telaprevir-based therapy that are observed in treatment-experienced patients are owing to a poorer response to pegIFN/RBV than in treatment-naive patients, resulting in the subsequent outgrowth of resistant variants selected by boceprevir or telaprevir. "
"The clinical implications of treatment failure to boceprevir- or telaprevir-based therapy are unknown. In theory, the persistence of resistant variants could lead to patients being ineligible for, or unresponsive to, future regimens that incorporate PIs into novel regimens. Several lines of evidence and reasoning provide reassurance on this issue. First, HCV is not known to be capable of archiving its genome as do HIV or hepatitis B virus. Data suggest that after treatment withdrawal, treatment-emergent substitutions decline in relative abundance over time and that wild-type virus regains its predominance in the majority of cases.[55-57] However, this may take 2-3 years, and subtype 1a tends to return to wild type more slowly. Moreover, the diversity of antiviral agents under development may overcome whatever adverse impact viral variants that are resistant to boceprevir or telaprevir might confer. Ultimately, trials in patients who have failed boceprevir or telaprevir therapy will be critical in addressing this question.
The panel underscored the importance of assessing the indications for treatment (particularly in null responders—weighing risk of treatment failure and resistance with need for therapy), adherence to stopping rules to minimize the risk of emergence of resistant variants, and any potential impact on future treatment options. For both drugs, the stopping rules put forth in the prescribing information have been harmonized for treatment-naive and treatment-experienced patients. Of note, the HCV RNA cutoffs used for boceprevir and telaprevir stopping rules differ. .....
Currently, there is no evidence to support switching from one PI to the other if treatment is not successful. The safety and efficacy of switching to the other PI because of a drug-specific adverse event also has not been established. Likewise, a patient for whom one PI was not successful should not be retreated with a regimen containing the other PI."
It appears you had a breakthrough. You should wait for the viral load to rise to make sure there wasn't an error on the lab test first.
Sorry but you can NOT treat with Victrelis or Incivek again. You have developed resistance to the drug.
From the Incivek label "There are no clinical data on re-treating patients who have failed an HCV NS3/4A protease inhibitor-based treatment, nor are there data on repeated courses of INCIVEK."
"...because new antiviral drugs directly inhibit hepatitis C virus, viral resistance has become an important issue, essentially precluding use of protease inhibitor monotherapy, and potentially restricting future treatment options for patients who consequently do not achieve sustained virological response."
"Persistence of Resistance-Associated Substitutions
Data from an ongoing, long-term follow-up study of subjects who did not achieve SVR in Phase 2 trials with VICTRELIS, with a median duration of follow-up of approximately 2 years, indicate that HCV populations harboring certain post-baseline, treatment-emergent substitutions may decline in relative abundance over time. However, among those subjects with available data, one or more treatmentemergent substitutions remained detectable with a population-based sequencing assay in 25% of subjects after 2.5 years of follow-up. The most common NS3 substitutions detected after 2.5 years of follow-up were T54S and R155K. The lack of detection of a substitution based on a population-based assay does not necessarily indicate that viral populations carrying that substitution have declined to a
background level that may have existed prior to treatment. The long-term clinical impact of the emergence or persistence of boceprevir-resistance-associated substitutions is unknown.
No data are available regarding the efficacy of VICTRELIS among subjects who were previously exposed to
VICTRELIS, or who previously failed treatment with a regimen containing VICTRELIS. "
You should try to get into a clinical trial that uses a non-protease inhibitor anti-viral drug.
Good luck!
Hector
Sorry but you can NOT treat with Victrelis or Incivek again. You have developed resistance to the drug.
From the Incivek label "There are no clinical data on re-treating patients who have failed an HCV NS3/4A protease inhibitor-based treatment, nor are there data on repeated courses of INCIVEK."
"...because new antiviral drugs directly inhibit hepatitis C virus, viral resistance has become an important issue, essentially precluding use of protease inhibitor monotherapy, and potentially restricting future treatment options for patients who consequently do not achieve sustained virological response."
"Persistence of Resistance-Associated Substitutions
Data from an ongoing, long-term follow-up study of subjects who did not achieve SVR in Phase 2 trials with VICTRELIS, with a median duration of follow-up of approximately 2 years, indicate that HCV populations harboring certain post-baseline, treatment-emergent substitutions may decline in relative abundance over time. However, among those subjects with available data, one or more treatmentemergent substitutions remained detectable with a population-based sequencing assay in 25% of subjects after 2.5 years of follow-up. The most common NS3 substitutions detected after 2.5 years of follow-up were T54S and R155K. The lack of detection of a substitution based on a population-based assay does not necessarily indicate that viral populations carrying that substitution have declined to a
background level that may have existed prior to treatment. The long-term clinical impact of the emergence or persistence of boceprevir-resistance-associated substitutions is unknown.
No data are available regarding the efficacy of VICTRELIS among subjects who were previously exposed to
VICTRELIS, or who previously failed treatment with a regimen containing VICTRELIS. "
You should try to get into a clinical trial that uses a non-protease inhibitor anti-viral drug.
Good luck!
Hector
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